Asenapine maleate

Base Information

• Chemical Name: Asenapine maleate
• CAS No.: 85650-56-2
• Molecular Formula: C21H20ClNO5
• Molecular Weight: 401.847
• Hs Code.: 29339900
• European Community (EC) Number: 288-064-8
• UNII: CU9463U2E2
• DSSTox Substance ID: DTXSID301017360
• Wikidata: Q27139467
• NCI Thesaurus Code: C79727
• RXCUI: 860647
• Mol file: 85650-56-2.mol

Synonyms:5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz(2,3-6,7)oxepino(4,5-c)pyrrole;Asenapine;asenapine maleate;ORG 5222;ORG-5222;saphris;Secuado;trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz(2,3:6,7)oxepino(4,5-c)pyrrole

Chemical Property of Asenapine maleate

Chemical Property:

• Vapor Pressure: 2.65E-05mmHg at 25°C
• Melting Point: 141-145°
• Boiling Point: 357.9 °C at 760 mmHg
• PKA: pK1 <3, pK2 7.52, pK3 8.51(at 25℃)
• Flash Point: 170.2 °C
• PSA: 87.07000
• LogP: 3.90820
• Storage Temp.: 2-8°C
• Solubility.: H2O: ≥10mg/mL
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 2
• Exact Mass: 401.1030004
• Heavy Atom Count: 28
• Complexity: 482

Purity/Quality:

98%min ^*data from raw suppliers

Asenapine maleate ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn, N
• Hazard Codes: Xn,N,T,F
• Statements: 22-36/37/38-50/53-39/23/24/25-23/24/25-11
• Safety Statements: 26-60-61-45-36/37-16

MSDS Files:

Useful:

• Canonical SMILES: CN1CC2C(C1)C3=C(C=CC(=C3)Cl)OC4=CC=CC=C24.C(=CC(=O)O)C(=O)O
• Isomeric SMILES: CN1C[C@H]2[C@H](C1)C3=C(C=CC(=C3)Cl)OC4=CC=CC=C24.C(=C\C(=O)O)\C(=O)O
• Recent ClinicalTrials: Bio-equivalence Study Between SAPHRIS and Asenapine
• Recent EU Clinical Trials: A Multicenter, Double-Blind, Fixed-Dose, Long-Term Extension Trial
• Description: Asenapine, a dual antagonist of dopamine D2and serotonin 5-HT2receptors, was launched for the acute treatment of schizophreniaand manic or mixed episodes associated with bipolar I disorder in adults. Asenapine exhibits high affinity for serotonin 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5, 5-HT6, and 5-HT7 receptors (Ki = 2.5, 4.0, 0.06, 0.16, 0.03, 1.6, 0.25, and 0.13 nM, respectively); dopamine D1, D2, D3, and D4 receptors (Ki = 1.4, 0.42, 1.1, and 1.3 nM, respectively); a1- and a2-adrenergic receptors (Ki = 1.2 and 1.2 nM, respectively); and histamine H1 receptors (Ki = 1.0 nM), and moderate affinity for H2 receptors (Ki = 6.2 nM). In in vitro assays, asenapine acts as an antagonist at these receptors. Asenapine has no appreciable affinity for muscarinic cholinergic receptors (e.g., Ki = 8128 nM for M1). Despite its potent binding affinity for multiple receptors, the efficacy of asenapine in schizophrenia is thought to be primarily mediated through a combination of antagonist activity at D2 and 5-HT2A receptors.
• Uses: Antipsychotic;serotonin 5-HT receptors Asenapine Maleate is a 5-HT receptor antagonist developed for the treatment of acute schizophrenia and bipolar mania. Asenapine maleate has been used as a stressor in studying the Fos expression in forebrain structures of rat models.

Technology Process of Asenapine maleate

There total 41 articles about Asenapine maleate which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 98.86%

asenapine (65576-45-6,65621-78-5) + maleic acid (110-16-7,26099-09-2) → trans-5-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz<2,3:6,7>oxepino<4,5-c>pyrrolidine maleate (85650-56-2,85650-55-1)

Guidance literature:

In ethanol; tert-butyl methyl ether; at 0 - 20 ℃; for 2h; Solvent; Temperature; Time;

Reference yield: 52.3%

formaldehyd (50-00-0,30525-89-4,61233-19-0) + trans-5-chloro-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrole hydrochloride (1170701-78-6) + maleic acid (110-16-7,26099-09-2) → trans-5-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz<2,3:6,7>oxepino<4,5-c>pyrrolidine maleate (85650-56-2,85650-55-1)

Guidance literature:

trans-5-chloro-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrole hydrochloride; With sodium hydroxide; In dichloromethane; water; pH=> 10;

formaldehyd; With formic acid; In water; toluene; at 60 ℃; for 2h;

maleic acid;

Reference yield:

asenapine phosphate + maleic acid (110-16-7,26099-09-2) → trans-5-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz<2,3:6,7>oxepino<4,5-c>pyrrolidine maleate (85650-56-2,85650-55-1)

Guidance literature:

asenapine phosphate; With sodium hydrogencarbonate; In toluene; at 25 ℃; for 0.5h; Industry scale;

maleic acid; In isopropyl alcohol; at 25 - 50 ℃; Industry scale;

upstream raw materials:

asenapine

maleic acid

2'-chloro-benzeneacetic acid

4-chloro-phenol

Downstream raw materials:

asenapine

5-Chloro-2-methyl-2H-8-oxa-2-aza-dibenzo[e,h]azulene

5-Chloro-2-methyl-8-oxa-2-aza-dibenzo[e,h]azulene-1,3-dione

trans-(3a,12b)-11-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]oxepino[4,5-C]pyrrol-1-one

Refernces

• 1、 -. "COMPRESSED ORAL DOSAGE FORM FOR ASENAPINE MALEATE". Page/Page column 28. . Retrieved 2013/04/10.
• 2、 -. "NOVEL PROCESS FOR THE PREPARATION OF ASENAPINE". Page/Page column 34. . Retrieved 2012/02/13.